Catecholamine activity in the CNS is now known to play a dominant role in the control of the onset and maintenance of normal mammalian reproductive function. The proposed research is designed to test the hypothesis that changes in catecholamine activity are responsible also for reproductive senescence. The experiments to be conducted include: (1) measurement of changes in neuroendocrine activity associated with various phases of reproductive life; (2) determination of causal relationships by controlled manipulation of endocrine and catecholamine activity. To accomplish these aims, complementary studies will be conducted in rats, humans, and sheep. Catecholaminergic neural activity will be quantified by determination of levels and turnover in circumscribed regions of the hypothalamus and pituitary and in CSF and plasma. Precisely defined areas of brain tissue will be obtained by microdissection. Norepinephrine, epinephrine, and dopamine will be measured by radioenzymatic assay. Since the causes and effects of catecholamine changes may involve the intermediation of other neuroendocrine factors, the concentrations of several factors functionally related to the catecholamines will be determined. These include LRF and selected pituitary and steroid hormones. The functional role of catecholamine changes during reproductive senescence will be studied by examining the effects of (1) surgical and/or immunological suppression of selected circulating hormones and (2) treatments with specific hormones and/or adrenergic drugs on catecholaminergic activity and on cyclicity. These studies will provide significant insights into the normal regulation of reproductive cycles and the mechanisms underlying senescent anovulation. These insights may lead to superior methods of fertility control and to improved clinical management of menopausal symptoms and related disorders.